Antibodies specific for carcinogen-DNA adducts have probed the nature, extent and consequences of in vitro and in vivo DNA modification. Biological samples of DNA substituted with 2-acetylaminofluorene (AAF), benzo(a)pyrene (BP) or cis-dichlorodiammineplatinum (II) (cis-DDP) were subjected to immunological localization and quantitative immunoassays able to detect one adduct in one hundred million nucleotides. In hepatic DNA of rats fed a carcinogenic level of AAF for 4 weeks, adduct accumulation reached a plateau at 2-3 weeks. During 4 subsequent weeks on control diet, adduct removal was biphasic with a rapid initial phase followed by a slow second phase. A pharmacokinetic model consistent with this data proposes that adducts are formed in two DNA compartments, one from which adducts are removed rapidly and another from which adducts are removed slowly. Persistent adducts accumulate in the slow-repairing compartment, but constitute less than 7% of the total adducts formed. In contrast to the high levels of AAF adducts in liver DNA, binding of BP to deoxyguanosine in DNA of mouse epidermis and cultured epidermal cells was more than 50-fold lower. Binding levels were similar in epidermis and epidermal cells, subsequent to dosages known to induce papillomas in vivo and differentiation-altered foci in the cultured keratinocytes. The kinetics of repair for BPdG in vivo and in vitro were biphasic (as in liver) but much more rapid, with 50% removal by 1-2 days. Thus, adduct accumulation and removal seem to be characteristic of interaction between a particular target tissue and an individual carcinogen, and may not be quantitatively related to efficiency of tumorigenesis or transformation. Antisera specific for cis-DDP-DNA (bidentate N-7 dideoxyguanosine intrastrand adduct) have been used to measure adducts in DNA of nucleated blood cells from cancer patients on platinum drug chemotherapy. Adducts appear to accumulate both as a function of total cumulative dose and increasing cycle number in individuals who have not received previous platinum drug therapy. The relationship between ability to form adducts, and disease response, appears promising.